@article {Didion024851, author = {John P Didion and Andrew P Morgan and Liran Yadgary and Timothy A Bell and Rachel C McMullan and Lydia Ortiz de Solorzano and Janice Britton-Davidian and Carol J Bult and Karl J Campbell and Riccardo Castiglia and Yung-Hao Ching and Amanda J Chunco and James J Crowley and Elissa J Chesler and John E French and Sofia I Gabriel and Daniel M Gatti and Theodore Garland, Jr. and Eva B Giagia-Athanasopoulou and Mabel D Gim{\'e}nez and Sofia A Grize and {\.I}slam G{\"u}nd{\"u}z and Andrew Holmes and Heidi C Hauffe and Jeremy S Herman and James M Holt and Kunjie Hua and Wesley J Jolley and Anna K Lindholm and Mar{\'\i}a J L{\'o}pez-Fuster and George Mitsainas and Maria Mathias and Leonard McMillan and M Gra{\c c}a Ramalhinho and Barbara Rehermann and Stephan P Rosshart and Jeremy B Searle and Meng-Shin Shiao and Emanuela Solano and Karen L Svenson and Pat Thomas-Laemont and David W Threadgill and Jacint Ventura Queija and George M Weinstock and Daniel Pomp and Gary A Churchill and Fernando Pardo-Manuel de Villena}, title = {R2d2 drives selfish sweeps in the house mouse}, elocation-id = {024851}, year = {2015}, doi = {10.1101/024851}, publisher = {Cold Spring Harbor Laboratory}, abstract = {A selective sweep is the result of strong positive selection rapidly driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population or species. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little empirical evidence addresses whether {\textquotedblleft}selfish{\textquotedblright} genes are capable of fixation -- thereby leaving signatures identical to classical selective sweeps -- despite being neutral or deleterious to organismal fitness. We previously reported the discovery of R2d2, a large copy-number variant that causes non-random segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a {\textquotedblleft}selfish{\textquotedblright} sweep driven by alleles of R2d2 with high copy number (R2d2HC) in natural populations of mice. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2HC rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2HC is also associated with significantly reduced litter sizes in heterozygosity, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution.}, URL = {https://www.biorxiv.org/content/early/2015/10/14/024851}, eprint = {https://www.biorxiv.org/content/early/2015/10/14/024851.full.pdf}, journal = {bioRxiv} }